The objective is to identify mechanism of injury to brain and other organs caused by chronic ethanol ingestion. Methods to be employed include: 1) Use of chronic ethanol-fed and withdrawal rat model (2 or more months of continuous feeding of 30% ethanol solution and high protein, vitamin rich diet). 2) Measure norepinephrine (NE) receptor sensitivity of brain and other organs in vitro using the cAMP response assay. 3) Measure isoproterenol receptor sensitivity of various organs in vivo using the cAMP response and Ca2 ion flux assay. 4) Measure response of subcellular organelles including mitrochondria in brain and other organs using the cAMP response assay and Ca2 ion flux in vivo and in vitro. 5) Measure the responsiveness of various organs and subcellular organelles to glucagon and other transmitters in vitro using the cAMP response assay. 6) Test the hypothesis that the locus coeruleus (L.C.) is stimulated to fire excessively as a result of chronic ethanol-feeding and withdrawal using stereotaxically placed electrodes in the area of the L.C. 7) Lesion the L.C. on one side and test both cerebral cortices for subsensitivity and supersensitivity using the cAMP response to NE in vitro. 8) Measure the Ca2 ion flux and adenyl cyclase response to in vivo isoproterenol electron microscopic cytochemical techniques in various organs.